Crystalline silica was previously shown to bind to DNA in vitro by analysis of modified spectra of silica, DNA and their combination, obtained by attenuated reflectance Fourier transform infrared spectroscopy (ATR FR-IR). Hydrogen bonding between the phosphate backbone of DNA and the silanol groups (SiOH) on the silica surface was indicated by this method. The mechanisms and pathways of this critical interaction were investigated. Binding of the hydrogen acceptor 2-PVPNO [poly(2-vinylpyridine-N-oxide)] to silanol groups was found to block quartz binding to DNA. Different crystalline silica samples, evaluated in relation to their surface area, were compared for their respective levels of (a) induced DNA damage in vitro (measured by gel electrophoresis and by gas chromatography-mass spectrometry) and (b) surface reactivity (measured by electron spin resonance (ESR) spin trapping and by oxygen consumption). The order of activity of the samples differed for (a) and (b), and was affected by the presence or absence of hydrogen peroxide. The role of metal iron on the silica surface in a Fenton type reaction was further demonstrated by showing that quartz-induced DNA damage is enhanced by adding ferric chloride and inhibited by iron chelators. The role of iron is proposed as a major factor in the induction of DNA damage by crystalline silica. The quartz sample F600, showing low cytotoxicity but significant induction of neoplastic transformation, was analyzed and found to contain l-2 wt% kaolinite and less than 0.5 wt% biotite. The role of metal impurities and of added minerals on silica toxicity and cell transformation is being studied further. All the crystalline silica samples were analized for Zeta potential and found negatively charged (average of about -60 +/- 5 mV). The dye, Janus Green B, was shown to adsorb to the crystalline silica surface in proportion to the surface area and to turn the charge on silica surface from negative to positive (+26 mV), indicating electrostatic binding of the dye to the silica surface and confirming the dye's usefulness as a measure of surface area and surface charge.